Scientific publications

Randomized phase II clinical trial of ruxolitinib plus simvastatin in COVID19 clinical outcome and cytokine evolution

Apr 13, 2023 | Magazine: 10.3389/fimmu.2023.1156603

Jesus Garcia-Donas 1, Diego Martínez-Urbistondo 2, Kyra Velázquez Kennedy 3, Paula Villares 2, Arántzazu Barquin 1, Andrea Dominguez 2, Juan Francisco Rodriguez-Moreno 1, Elena Caro 2, Rafael Suarez Del Villar 2, Estanislao Nistal-Villan 4 5, Monica Yagüe 6, Maria Ortiz 7, Maria Barba 6, Sergio Ruiz-Llorente 6, Miguel Quiralte 6, Massimiliano Zanin 8, Cristina Rodríguez 9, Paloma Navarro 6, Pedro Berraondo 10 11 12, Rodrigo Madurga 13


Background: Managing the inflammatory response to SARS-Cov-2 could prevent respiratory insufficiency. Cytokine profiles could identify cases at risk of severe disease.

Methods: We designed a randomized phase II clinical trial to determine whether the combination of ruxolitinib (5 mg twice a day for 7 days followed by 10 mg BID for 7 days) plus simvastatin (40 mg once a day for 14 days), could reduce the incidence of respiratory insufficiency in COVID-19. 48 cytokines were correlated with clinical outcome.

Participants: Patients admitted due to COVID-19 infection with mild disease.

Results: Up to 92 were included. Mean age was 64 ± 17, and 28 (30%) were female. 11 (22%) patients in the control arm and 6 (12%) in the experimental arm reached an OSCI grade of 5 or higher (p = 0.29). Unsupervised analysis of cytokines detected two clusters (CL-1 and CL-2). CL-1 presented a higher risk of clinical deterioration vs CL-2 (13 [33%] vs 2 [6%] cases, p = 0.009) and death (5 [11%] vs 0 cases, p = 0.059). Supervised Machine Learning (ML) analysis led to a model that predicted patient deterioration 48h before occurrence with a 85% accuracy.

Conclusions: Ruxolitinib plus simvastatin did not impact the outcome of COVID-19. Cytokine profiling identified patients at risk of severe COVID-19 and predicted clinical deterioration.

CITA DEL ARTÍCULO Front Immunol. 2023 Apr 18:14:1156603. doi: 10.3389/fimmu.2023.1156603. eCollection 2023.